This Program Project conducts a comprehensive analysis of the mechanism(s) of HIV latency and viral reservoirs. In vitro investigations in tissue culture systems (Projects 1, 2, and 3) will be closely coordinated with in vivo studies in Core B ("Non-human Primates for HIV/SIV Reservoirs and Latency"). Accordingly, Core B will provide rhesus macaques and appropriate infrastructure support required for the animal model studies in this Program Project. This Core uses macaques housed at the California National Primate Research Center (CNPRC) at UC Davis. This Center is accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC) and includes full-time, licensed veterinarians. Appropriate facilities and expertise are available for the care and handling of macaques inoculated with SIV/SHIV at biosafety levels 2 and 3 (BSL-2, -3). In addition, the CNPRC infrastructure and staff provide for clinical analysis of infected animals;this includes physical diagnosis, microbiological analysis, and hematological assessments. Veterinary pathologists perform comprehensive necropsy and pathology analysis and to collect tissues and organs for all of the projects in this Program. Several studies on antiretroviral drugs, in the SIV/macaque and RTSHIV/ macaque systems, have been conducted at the CNPRC;thus, this Core builds on demonstrated strengths that are directly relevant to the goals of the Program Project. For the studies in Core B, we hypothesize that the macaque model of SIV/SHIV infection can be used to define viral reservoirs, to analyze latency, and to study activation of virus in vivo. Three Specific Aims address this hypothesis: Aim 1: to define conditions in the SIV/macaque and RT-SHIV/macaque systems for analysis of viral latency/reservoirs as observed in humans infected with HIV;Aim 2: to analyze virus localization in infected macaques undergoing antiretroviral therapy;Aim 3: to determine the role of viral and host-cell factors in the regulation of viral latency, persistence, and reactivation.